Posted by ed_uk on January 3, 2005, at 22:20:33
In reply to Re: TCAs-maprotiline » banga, posted by KaraS on January 3, 2005, at 22:00:48
I think I may have made a mistake about maprotiline and weight gain :-( Don't think it's too bad in the sexual department though!
Here is some info. The risk of skin rashes and seizures is emphasized.
Adverse Effects, Treatment, and Precautions
Adverse effects with maprotiline, a tetracyclic antidepressant, are broadly similar to those with tricyclic antidepressants (see Amitriptyline, ) but antimuscarinic effects are less frequent.Skin rashes seem more common with maprotiline than with tricyclic antidepressants. Seizures have occurred in patients with no prior history of such disorders as well as in those with a history of epilepsy and the risk is increased if high doses of maprotiline are employed. It should not be used in patients with epilepsy or a lowered seizure threshold.
Incidence of adverse effects.
By March 1985 the UK Committee on Safety of Medicines1 had received reports of the following adverse reactions associated with maprotiline from a cumulative total of 2.5 million prescriptions: convulsions (124 cases), hepatic reactions (4 cases), and haematological reactions (8 cases). There had also been 454 reports of skin rashes.1. Committee on Safety of Medicines. Dangers of newer antidepressants. Current Problems 15 1985.
Effects on the skin.
In addition to many recorded instances of skin rashes with maprotiline (see ) cutaneous vasculitis, which resolved on discontinuation of therapy, has also been observed.11. Oakley AMM, Hodge L. Cutaneous vasculitis from maprotiline. Aust N Z J Med 1985; 15: 256–7. PubMed
Epileptogenic effect.
In a retrospective review of 186 psychiatric patients with no history of seizures, 5 of 32 patients receiving maprotiline developed generalised tonic-clonic seizures, compared with 1 of 45 receiving a tricyclic antidepressant.1 There were no seizures in the remaining patients who received other medications, or no drug treatment. Two of the 5 patients experiencing seizures with maprotiline were receiving doses of 75 to 150 mg daily, 2 were receiving daily doses of 200 to 300 mg, and one patient experienced partial complex seizures with a daily dose of 150 mg and generalised tonic-clonic seizures after increasing the daily dose to 300 mg.1. Jabbari B, et al Incidence of seizures with tricyclic and tetracyclic antidepressants. Arch Neurol 1985; 42: 480–1. PubMed
Overdosage.
Apart from seizures being more common with maprotiline, features of overdosage are similar to those experienced with tricyclic antidepressant poisonings (see under Adverse Effects of Amitriptyline, ).For a discussion of choice of antidepressant with respect to toxicity in overdosage, see under Depression, .
References.
1. Crome P, Newman B. Poisoning with maprotiline and mianserin. BMJ 1977; 2: 260. PubMed
2. Curtis RA, et al. Fatal maprotiline intoxication. Drug Intell Clin Pharm 1984; 18: 716–20. PubMed
3. Knudsen K, Heath A. Effects of self poisoning with maprotiline. BMJ 1984; 288: 601–3. PubMed
4. Crome P, Ali C. Clinical features and management of self-poisoning with newer antidepressants. Med Toxicol 1986; 1: 411–20. PubMed
Porphyria.
Maprotiline hydrochloride is considered to be unsafe in patients with porphyria because it has been shown to be porphyrinogenic in animals.Interactions
Interactions associated with maprotiline are similar to those associated with tricyclic antidepressants (see Amitriptyline, ).Pharmacokinetics
Maprotiline is slowly but completely absorbed from the gastrointestinal tract. It is widely distributed throughout the body and is extensively bound to plasma protein.Maprotiline is extensively demethylated in the liver to its principal active metabolite, desmethylmaprotiline; paths of metabolism of both maprotiline and desmethylmaprotiline include N-oxidation, aliphatic and aromatic hydroxylation, and the formation of aromatic methoxy derivatives. In addition to desmethylmaprotiline, maprotiline-N-oxide is also reported to be pharmacologically active. The average elimination half-life of maprotiline is reported to be about 43 hours and that of its active metabolite even longer (range 60 to 90 hours). Maprotiline is excreted in the urine, mainly in the form of its metabolites, either in free or in conjugated form; appreciable amounts are also excreted in the faeces.
Maprotiline is distributed into breast milk (see Breast Feeding under Precautions of Amitriptyline, ).
References.
1. Maguire KP, et al An evaluation of maprotiline: intravenous kinetics and comparison of two oral doses. Eur J Clin Pharmacol 1980; 18: 249–54. PubMed
2. Alkalay D, et al. Bioavailability and kinetics of maprotiline. Clin Pharmacol Ther 1980; 27: 697–703. PubMed
3. Firkusny L, Gleiter H. Maprotiline metabolism appears to co-segregate with the genetically-determined CYP2D6 polymorphic hydroxylation of debrisoquine. Br J Clin Pharmacol 1994; 37: 383–8. PubMed
Uses and Administration
Maprotiline is a tetracyclic antidepressant with actions and uses similar to those of tricyclic antidepressants (see Amitriptyline, ). It is one of the more sedating antidepressants but antimuscarinic effects are less marked. Like the tricyclics, maprotiline is an inhibitor of the reuptake of noradrenaline; it also has weak affinity for central adrenergic (α1) receptors.Maprotiline is usually given by mouth as the hydrochloride but it has also been given by injection as the mesilate and in oral drops as the resinate.
In the treatment of depression () maprotiline hydrochloride is given by mouth in doses of 25 to 75 mg daily in three divided doses, gradually increased to 150 mg daily if necessary; up to 225 mg daily may be required in severely depressed patients in hospital. The dosage should be adjusted after 1 or 2 weeks according to response. Because of the prolonged half-life of maprotiline the total daily dose may also be given as a single dose, usually at night. A suggested initial dose for elderly patients is 10 mg three times daily or 30 mg at night gradually increased according to response over a period of 1 to 2 weeks to 25 mg three times daily or 75 mg at night.
Maprotiline should be withdrawn gradually to reduce the risk of withdrawal symptoms.
Preparations
Single-ingredient Preparations
The symbol ¤ denotes a preparation which is discontinued or no longer actively marketed.Austria: Ludiomil; Belg.: Ludiomil; Braz.: Ludiomil; Canad.: Ludiomil; Denm.: Ludiomil; Maludil; Fr.: Ludiomil; Ger.: Aneural¤; Delgian¤; Depressase¤; Deprilept; Kanopan¤; Ludiomil; Mapro-GRY¤; Mapro-Tablinen¤; Maprolu; Mirpan¤; Psymion¤; Gr.: Aprotilin; Ludiomil; Hong Kong: Ludiomil; Hung.: Ludiomil; Maprolu; Irl.: Ludiomil¤; Israel: Ludiomil¤; Melodil; Ital.: Ludiomil; Maprolit¤; Malaysia: Ludiomil; Mex.: Ludiomil; Neth.: Ludiomil; NZ: Ludiomil; Port.: Ludiomil; S.Afr.: Ludiomil; Singapore: Ludiomil; Spain: Ludiomil; Swed.: Ludiomil; Switz.: Ludiomil¤; Ludiomil; Ludiomil; Thai.: Ludiomil; UK: Ludiomil; USA: Ludiomil¤;
Pharmacopoeial Preparations
USP 27: Maprotiline Hydrochloride Tablets;
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